Tandem tudor domain within UHRF1; TTD, tandem tudor domain within UHRF1 preferentially binds H3 histone tails trimethylated at Lys-9. It specifically recognizes H3 tail peptides with the heterochromatin-associated modification state of trimethylated lysine 9 and unmodified lysine 4 (H3K4me0/K9me3). This domain is found in eukaryotes and is found in association with pfam00097, pfam02182, pfam00628, pfam00240.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  128 LGLYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEDEPCSSSAVKTSEDDIMYHVKYDDYPEHGVDIVKAKNVRARARTV 207
Cdd:pfam12148   1 KGLYKINELVDARDVSIGAWFEAKIVKVTKDKDSKDESTSNSDSSTSEEDVIYHVKYDDYPENGVVEMKLKDIRPRARTI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 162287241  208 IPWENLEVGQVVMANYNVDYPRKRGFWYDVEICRKRQTRTARELYGNIRLLNDS-QLNNCRIMFVDEVLMIELPK 281
Cdd:pfam12148  81 LKWDDLKVGQVVMVNYNPDEPKERGFWYDAEITEKKETRTSKELYGKILLGGDGdVLNDCKIKFVDEIFKIEEPG 155

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 162287241   1 MWIQVRTMDGKETHTVNSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVR 74
Cdd:cd17122    1 MWIQVRTMDGKETHRIDSLSKLTKVEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLLVR 74

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein UHRF1 and UHRF2; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 162287241 314 ACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCPSC 360
Cdd:cd15525    1 ACHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDDEWYCPDC 47

Tandem tudor domain within UHRF1; TTD, tandem tudor domain within UHRF1 preferentially binds H3 histone tails trimethylated at Lys-9. It specifically recognizes H3 tail peptides with the heterochromatin-associated modification state of trimethylated lysine 9 and unmodified lysine 4 (H3K4me0/K9me3). This domain is found in eukaryotes and is found in association with pfam00097, pfam02182, pfam00628, pfam00240.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  128 LGLYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEDEPCSSSAVKTSEDDIMYHVKYDDYPEHGVDIVKAKNVRARARTV 207
Cdd:pfam12148   1 KGLYKINELVDARDVSIGAWFEAKIVKVTKDKDSKDESTSNSDSSTSEEDVIYHVKYDDYPENGVVEMKLKDIRPRARTI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 162287241  208 IPWENLEVGQVVMANYNVDYPRKRGFWYDVEICRKRQTRTARELYGNIRLLNDS-QLNNCRIMFVDEVLMIELPK 281
Cdd:pfam12148  81 LKWDDLKVGQVVMVNYNPDEPKERGFWYDAEITEKKETRTSKELYGKILLGGDGdVLNDCKIKFVDEIFKIEEPG 155

SAD/SRA domain; The domain goes by several names including SAD, SRA and YDG. It adopts a beta barrel, modified PUA-like, fold that is widely present in eukaryotic chromatin proteins and in bacteria. Versions of this domain are known to bind hemi-methylated CpG dinucleotides and also other 5mC containing dinucleotides. The domain binds DNA by flipping out the methylated cytosine base from the DNA double helix.The conserved tyrosine and aspartate residues and a glycine rich patch are critical for recognition of the flipped out base. Mammalian UHRF1 that contains this domain plays an important role in maintenance of methylation at CpG dinucleotides by recruiting DNMT1 to hemimethylated sites associated with replication forks. The SAD/SRA domain has been combined with other domains involved in the ubiquitin pathway on multiple occasions and such proteins link recognition of DNA methylation to chromatin-protein ubiquitination. The domain is also found in species that lack DNA methylation, such as certain apicomplexans, suggestive of other DNA-binding modes or functions. A highly derived and distinct version of the domain is also found in fungi where it is fused to AlkB-type 2OGFeDO domains. In bacteria, the domain is usually fused or associated with restriction endonucleases, many of which target methylated or hemi-methylated DNA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  414 HFGPIPGVPVGTMWRFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDNGNYFTYTGSGGRDLSGNKrtagQS 493
Cdd:pfam02182   1 RFGHVPGVEVGDIFSSRAELCVVGLHRPTQAGIDGMKSEGAYSIVLSGGYEDDEDNGDVLIYTGSGGRDNTKKK----QS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  494 SDQKLTNNNRALALNCHspinekgaeaedwrQGKPVRVVRnmkGGKHSKYAPAEGNRYDGIYKVVKYWPERGKSGFLVWR 573
Cdd:pfam02182  77 ADQKLERGNLALANSCE--------------TGNPVRVIR---GSKRDSYPPKKGYRYDGLYKVEKYWEEKGKSGFLVFK 139

                  ....*..
gi 162287241  574 YLLRRDD 580
Cdd:pfam02182 140 FKLRRLP 146

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1); UHRF1, also known as inverted CCAAT box-binding protein of 90 kDa, nuclear protein 95, nuclear zinc finger protein Np95 (Np95), RING finger protein 106, transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also a N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) domain, a SET and RING finger associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitylation has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD domain targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-HC finger exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241 689 DGPYqiFLSKVKEAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVFSCPACRFELDHSSPTRVNQPLQTILNQLFP 768
Cdd:cd16769    1 PFQL--FLSKVEETFQCICCQELVFRPITTVCQHNVCKDCLDRSFRAQVFSCPACRYDLGRSYAMQVNQPLQTVLNQLFP 78

                 ....*.
gi 162287241 769 GYGSGR 774
Cdd:cd16769   79 GYGNGR 84

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein UHRF1 and UHRF2; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 162287241 314 ACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCPSC 360
Cdd:cd15525    1 ACHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDDEWYCPDC 47

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 162287241  315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVP-PEPEWYCPSCR 361
Cdd:pfam00628   2 CAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEiPSGEWLCPECK 49

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 162287241     3 IQVRTMDGKE-THTVNslsRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVR 74
Cdd:smart00213   3 LTVKTLDGKTiTLEVK---PSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 162287241  696 LSKVKEAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVfSCPACRFElDHSSPTRVNqplqTILNQLFPGYGSGR 774
Cdd:TIGR00599  20 LYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQP-KCPLCRAE-DQESKLRSN----WLVSEIVESFKNLR 92

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241 705 CICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVFsCPACRFEldhssPTRVNQPLQTILNQLFPGYGSGR 774
Cdd:COG5432   28 CRICDCRISIPCETTCGHTFCSLCIRRHLGTQPF-CPVCRED-----PCESRLRGSSGSREINESHARNR 91

Tandem tudor domain within UHRF1; TTD, tandem tudor domain within UHRF1 preferentially binds H3 histone tails trimethylated at Lys-9. It specifically recognizes H3 tail peptides with the heterochromatin-associated modification state of trimethylated lysine 9 and unmodified lysine 4 (H3K4me0/K9me3). This domain is found in eukaryotes and is found in association with pfam00097, pfam02182, pfam00628, pfam00240.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  128 LGLYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEDEPCSSSAVKTSEDDIMYHVKYDDYPEHGVDIVKAKNVRARARTV 207
Cdd:pfam12148   1 KGLYKINELVDARDVSIGAWFEAKIVKVTKDKDSKDESTSNSDSSTSEEDVIYHVKYDDYPENGVVEMKLKDIRPRARTI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 162287241  208 IPWENLEVGQVVMANYNVDYPRKRGFWYDVEICRKRQTRTARELYGNIRLLNDS-QLNNCRIMFVDEVLMIELPK 281
Cdd:pfam12148  81 LKWDDLKVGQVVMVNYNPDEPKERGFWYDAEITEKKETRTSKELYGKILLGGDGdVLNDCKIKFVDEIFKIEEPG 155

SAD/SRA domain; The domain goes by several names including SAD, SRA and YDG. It adopts a beta barrel, modified PUA-like, fold that is widely present in eukaryotic chromatin proteins and in bacteria. Versions of this domain are known to bind hemi-methylated CpG dinucleotides and also other 5mC containing dinucleotides. The domain binds DNA by flipping out the methylated cytosine base from the DNA double helix.The conserved tyrosine and aspartate residues and a glycine rich patch are critical for recognition of the flipped out base. Mammalian UHRF1 that contains this domain plays an important role in maintenance of methylation at CpG dinucleotides by recruiting DNMT1 to hemimethylated sites associated with replication forks. The SAD/SRA domain has been combined with other domains involved in the ubiquitin pathway on multiple occasions and such proteins link recognition of DNA methylation to chromatin-protein ubiquitination. The domain is also found in species that lack DNA methylation, such as certain apicomplexans, suggestive of other DNA-binding modes or functions. A highly derived and distinct version of the domain is also found in fungi where it is fused to AlkB-type 2OGFeDO domains. In bacteria, the domain is usually fused or associated with restriction endonucleases, many of which target methylated or hemi-methylated DNA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  414 HFGPIPGVPVGTMWRFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDNGNYFTYTGSGGRDLSGNKrtagQS 493
Cdd:pfam02182   1 RFGHVPGVEVGDIFSSRAELCVVGLHRPTQAGIDGMKSEGAYSIVLSGGYEDDEDNGDVLIYTGSGGRDNTKKK----QS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241  494 SDQKLTNNNRALALNCHspinekgaeaedwrQGKPVRVVRnmkGGKHSKYAPAEGNRYDGIYKVVKYWPERGKSGFLVWR 573
Cdd:pfam02182  77 ADQKLERGNLALANSCE--------------TGNPVRVIR---GSKRDSYPPKKGYRYDGLYKVEKYWEEKGKSGFLVFK 139

                  ....*..
gi 162287241  574 YLLRRDD 580
Cdd:pfam02182 140 FKLRRLP 146

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 162287241   1 MWIQVRTMDGKETHTVNSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVR 74
Cdd:cd01797    1 MWIQVRTMDGKKEARVDGLSKLTKIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVGLNDIIQLMVR 74

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2, also termed Np95/ICBP90-like RING finger protein (NIRF), or Np95-likeRING finger protein, or nuclear protein 97, or nuclear zinc finger protein Np97, or RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131(ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 162287241   1 MWIQVRTMDGKETHTVNSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVR 74
Cdd:cd17123    1 MWIQVRTIDGTETQTIDDLSRLTKIESLREKIQELFNVRPERQRLFYRGKQLEDGHTLFDYNVGLNDIVQLLIR 74

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2, also known as Np95/ICBP90-like RING finger protein (NIRF), Np95-like RING finger protein, nuclear protein 97, nuclear zinc finger protein Np97, RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) domain, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 162287241 700 KEAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVFSCPACRFELDHSSPTRVNQPLQTILN 764
Cdd:cd16770    1 EESFLCICCQELVYQPVTTECQHNVCKSCLQRSFKAEVYTCPACRHDLGKNYSMVPNKILQTLLD 65

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein UHRF1 and UHRF2; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 162287241 314 ACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCPSC 360
Cdd:cd15525    1 ACHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDDEWYCPDC 47

second Tudor domain found in the UHRF (ubiquitin-like PHD and RING finger domain-containing protein) family; The UHRF family includes UHRF1 and UHRF2. UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain(PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger. The model corresponds to the second Tudor domain. The tandem Tudor domain directs binding of UHRF to the heterochromatin mark histone H3K9me3.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 162287241 210 WENLEVGQVVMANYNVDYPRKRGFWYDVEICRKRQTRTARELYGNIRLLNDSQ-LNNCRIMFVDEVLMIELP 280
Cdd:cd20388    1 WDDLKVGQTVMVNYNIDDPKERGYWYDAEITKKRNTRTKKELTGTLYLGPDLTpLEDCRIKFVDEIFKIEKP 72

first Tudor domain found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2) and similar proteins; UHRF2, also called Np95/ICBP90-like RING finger protein (NIRF), Np95-like RING finger protein, nuclear protein 97, nuclear zinc finger protein Np97, RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. UHRF2 also functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) domain, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger domain. The model corresponds to the first Tudor domain. The tandem Tudor domain directs binding of UHRF to the heterochromatin mark histone H3K9me3.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241 125 DTDLGLYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEdepCSSSAVKTSEDDIMYHVKYDDYPEHGVDIVKAKNVRARA 204
Cdd:cd20456   11 DPGIGIYKINELVDARDVSIGAWFEAHIENVTRASTPS---TSNSDCMDADEDVIYHIKYDDYPENGVVEMDTGNLRPRA 87

                 ....
gi 162287241 205 RTVI 208
Cdd:cd20456   88 RTIL 91

first Tudor domain found in the UHRF (ubiquitin-like PHD and RING finger domain-containing protein) family; The UHRF family includes UHRF1 and UHRF2. UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain(PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger. The model corresponds to the first Tudor domain. The tandem Tudor domain directs binding of UHRF to the heterochromatin mark histone H3K9me3.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 162287241 130 LYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEDEPCSssavktSEDDIMYHVKYDDYPEHGVDIVKAKNVRARARTVI 208
Cdd:cd20387    1 YYKVGDLVDARDPTMGAWFEAKIVRITKKEPNTNNKTA------DEDDLIYHVKFDDYEEEGPLEVSFKDIRPRARHLI 73

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 162287241    3 IQVRTMDGKeTHTVnSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVRQS 76
Cdd:pfam00240   1 ITVKTLDGK-KITL-EVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

PHD finger 1 found in Schizosaccharomyces pombe Lid2 complex component Lid2p and similar proteins; Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEpEWYCPSC 360
Cdd:cd15519    2 CEVCGLDDNEGEVLLCDGCDAEYHTSCLDPPLGEIPPG-TWFCPSC 46

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287241   3 IQVRTMDGKeTHTVnSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLL 72
Cdd:cd17039    1 ITVKTLDGK-TYTV-EVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

PHD finger found in bromodomain adjacent to zinc finger domain protein BAZ1A and BAZ1B; BAZ1A, also termed ATP-dependent chromatin-remodeling protein, or ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), or CHRAC subunit ACF1, or Williams syndrome transcription factor-related chromatin-remodeling factor 180 (WCRF180), or WALp1, is a subunit of the conserved imitation switch (ISWI)-family ATP-dependent chromatin assembly and remodeling factor (ACF)/chromatin accessibility complex (CHRAC) chromatin remodeling complex, which is required for DNA replication through heterochromatin. It alters the remodeling properties of the ATPase motor protein sucrose nonfermenting-2 homolog (SNF2H). Moreover, BAZ1A and its complexes play important roles in DNA double-strand break (DSB) repair. It is essential for averting improper gene expression during spermatogenesis. It also regulates transcriptional repression of vitamin D3 receptor-regulated genes. BAZ1B, also termed Tyrosine-protein kinase BAZ1B, or Williams syndrome transcription factor (WSTF), or Williams-Beuren syndrome chromosomal region 10 protein, Williams-Beuren syndrome chromosomal region 9 protein, or WALp2, is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. BAZ1B/WSTF, together with the imitation switch (ISWI) ATPase, forms a WSTF-ISWI chromatin remodeling complex (WICH), which transiently associates with the human inactive X chromosome (Xi) during late S-phase prior to BRCA1 and gamma-H2AX. Moreover, BAZ1B/WSTF, SNF2h, and nuclear myosin 1 (NM1) forms the chromatin remodeling complex B-WICH that is involved in regulating rDNA transcription. Both BAZ1A and BAZ1B contain a WAC motif, a DDT domain, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 162287241 314 ACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVpPEPEWYCPSC 360
Cdd:cd15544    1 RCKVCRKKGDPDNMILCDGCDKAFHLYCLRPALREV-PSGDWFCPAC 46

PHD finger found in PHD and RING finger domain-containing protein 1 (PHRF1); PHRF1, also termed KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase that induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEpEWYCPSC 360
Cdd:cd15536    2 CEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIE-EWFCPEC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) and 2B (BAZ2B); BAZ2A, also termed transcription termination factor I-interacting protein 5 (TTF-I-interacting protein 5, or Tip5), or WALp3, is an epigenetic regulator. It has been implicated in epigenetic rRNA gene silencing, as the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. BAZ2A has also been shown to be broadly overexpressed in prostate cancer, to regulate numerous protein-coding genes and to cooperate with EZH2 (enhancer of zeste homolog 2) to maintain epigenetic silencing at genes repressed in prostate cancer metastasis. Its overexpression is tightly associated with a prostate cancer subtype displaying CpG island methylator phenotype (CIMP) in tumors and with prostate cancer recurrence in patients. BAZ2B, also termed WALp4, is a bromodomain-containing protein whose biological role is still elusive. It shows high sequence similarly with BAZ2A. Both BAZ2A and BAZ2B contain a TAM (TIP5/ARBP/MBD) domain, a DDT domain, four AT-hooks, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain. BAZ2B also harbors an extra Apolipophorin-III like domain in its N-terminal region.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVpPEPEWYCPSC 360
Cdd:cd15545    2 CQICRSGDNEDQLLLCDGCDRGYHTYCFKPKMTNV-PEGDWFCPEC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 1B (BAZ1B); BAZ1B, also termed Tyrosine-protein kinase BAZ1B, or Williams syndrome transcription factor (WSTF), or Williams-Beuren syndrome chromosomal region 10 protein, Williams-Beuren syndrome chromosomal region 9 protein, or WALp2, is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. BAZ1B/WSTF, together with the imitation switch (ISWI) ATPase, forms a WSTF-ISWI chromatin remodeling complex (WICH), which transiently associates with the human inactive X chromosome (Xi) during late S-phase prior to BRCA1 and gamma-H2AX. Moreover, BAZ1B/WSTF, SNF2h, and nuclear myosin 1 (NM1) forms the chromatin remodeling complex B-WICH that is involved in regulating rDNA transcription. BAZ1B contains a WAC motif, a DDT domain, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPePEWYCPSC 360
Cdd:cd15628    2 CKVCRKKGEDDKLILCDECNQAFHLFCLRPALYEVPD-GEWMCPAC 46

PHD finger 2 found in d4 gene family proteins; The family includes proteins coded by three members of the d4 gene family, DPF1 (neuro-d4), DPF2 (ubi-d4/Requiem), and DPF3 (cer-d4), which function as transcription factors and are involved in transcriptional regulation of genes by changing the condensed/decondensed state of chromatin in the nucleus. DPF2 is ubiquitously expressed and it acts as a transcription factor that may participate in developmentally programmed cell death. DPF1 and DPF3 are expressed predominantly in neural tissues, and they may be involved in the transcription regulation of neuro-specific gene clusters. The d4 family proteins show distinct domain organization with domain 2/3 in the N-terminal region, a Cys2His2 (C2H2) zinc finger or Kruppel-type zinc finger in the central part and two adjacent plant homeodomain (PHD) fingers (d4-domain) in the C-terminal part of the molecule. This model corresponds to the second PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLtSVPPEPEWYCPSC 360
Cdd:cd15530    2 CSLCGTSENDDQLLFCDDCDRGYHMYCLSPPM-SEPPEGSWSCHLC 46

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 162287241 315 CHVCG-GREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCPSC 360
Cdd:cd15489    2 CIVCGkGGDLGGELLQCDGCGKWFHADCLGPPLSSFVPNGKWICPVC 48

PHD finger 1 found in Lysine-specific demethylase 5C (KDM5C) and 5D (KDM5D); The family includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C (also termed Histone demethylase JARID1C, Jumonji/ARID domain-containing protein 1C, SmcX, or Xe169) is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D (also termed Histocompatibility Y antigen (H-Y), Histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or SmcY) is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 andH3K4me2), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. Both KDM5C and KDM5D contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSvPPEPEWYCPSC 360
Cdd:cd15604    2 CRMCSRGDEDDKLLLCDGCDDNYHTFCLLPPLPE-PPKGIWRCPKC 46

PHD finger 2 found in monocytic leukemia zinc-finger protein (MOZ) and its factor (MORF); MOZ, also termed histone acetyltransferase KAT6A, YBF2/SAS3, SAS2 and TIP60 protein 3 (MYST-3), or runt-related transcription factor-binding protein 2, or zinc finger protein 220, is a MYST-type histone acetyltransferase (HAT) that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and p53-dependent transcription. It possesses intrinsic HAT activity to acetylate both itself and lysine (K) residues on histone H2B, histone H3 (K14) and histone H4 (K5, K8, K12 and K16) in vitro and H3K9 in vivo. MOZ-related factor (MORF), also termed MOZ2, or histone acetyltransferase KAT6B, or MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4 (MYST4), is a ubiquitously expressed transcriptional regulator with intrinsic HAT activity. It can interact with the Runt-domain transcription factor Runx2 and form a tetrameric complex with BRPFs, ING5, and EAF6. Both MOZ and MORF are catalytic subunits of HAT complexes that are required for normal developmental programs, such as hematopoiesis, neurogenesis, and skeletogenesis, and are also implicated in human leukemias. MOZ is also the catalytic subunit of a tetrameric inhibitor of growth 5 (ING5) complex, which specifically acetylates nucleosomal histone H3K14. Moreover, MOZ and MORF are involved in regulating transcriptional activation mediated by Runx2 (or Cbfa1), a Runt-domain transcription factor known to play important roles in T cell lymphomagenesis and bone development, and its homologs. MOZ contains a linker histone 1 and histone 5 domains and two plant homeodomain (PHD) fingers. In contrast, MORF contains an N-terminal region containing two PHD fingers, a putative HAT domain, an acidic region, and a C-terminal Ser/Met-rich domain. The family corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 162287241 314 ACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVpPEPEWYCPSC 360
Cdd:cd15527    1 TCSVCQDSGNADNLLFCDACDKGFHMECHDPPLTRM-PKGKWVCQIC 46

PHD finger 1 found in Lysine-specific demethylase 5A (KDM5A); KDM5A (also termed Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5A contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVpPEPEWYCPSC 360
Cdd:cd15602    2 CLFCGRGNNEDKLLLCDGCDDSYHTFCLIPPLPDV-PKGDWRCPKC 46

PHD finger 1 found in autoimmune regulator (AIRE); AIRE, also termed autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) protein, functions as a regulator of gene transcription in the thymus. It is essential for prevention of autoimmunity. AIRE plays a critical role in the induction of central tolerance. It promotes self-tolerance through tissue-specific antigen (TSA) expression. It also acts as an active regulator of chondrocyte differentiation. AIRE contains a homogeneously-staining region (HSR) or caspase-recruitment domain (CARD), a nuclear localization signal (NLS), a SAND (for Sp100, AIRE, nuclear phosphoprotein 41/75 or NucP41/75, and deformed epidermal auto regulatory factor 1 or Deaf1) domain, two plant homeodomain (PHD) fingers, and four LXXLL (where L stands for leucine) motifs. This model corresponds to the first PHD finger that recognizes the unmethylated tail of histone H3 and targets AIRE-dependent genes.

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                 ....*....|....*....|....*....|....*....|....*...
gi 162287241 315 CHVC--GGReapekQLLCDECDMAFHLYCLKPPLTSvPPEPEWYCPSC 360
Cdd:cd15539    2 CAVCgdGGE-----LLCCDGCPRAFHLACLVPPLTL-IPSGTWRCSSC 43

PHD finger 2 found in PHD finger protein 12 (PHF12), yeast Rco1, and similar proteins; PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This subfamily also includes yeast transcriptional regulatory protein Rco1 and similar proteins. Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two PHD fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the second PHD finger.

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gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCP 358
Cdd:cd15534    2 CFKCNRSCRVAPLIQCDYCPLLFHLDCLDPPLTHPPATGRWMCP 45

first RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the first one.

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gi 162287241 701 EAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVFSCPACR 744
Cdd:cd23138    1 DELNCSFCMQLPERPVTTPCGHNFCLKCFQKWMGQGKKTCGTCR 44

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 162287241 700 KEAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQ---VFSCPACR 744
Cdd:cd16597    3 EEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQhgsEYSCPQCR 50

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

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gi 162287241 704 QCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQV-FSCPACR 744
Cdd:cd16568    6 ECIICHEYLYEPMVTTCGHTYCYTCLNTWFKSNRsLSCPDCR 47

PHD finger 1 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The family includes two PCL family proteins, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are homologs of PHD finger protein1 (PHF1). PCL family proteins are accessory components of the polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. They specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD fingers of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the first PHD finger.

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gi 162287241 315 CHVCGGREAPEKQ--LLCDECDMAFHLYCLKPPLTSVPPEPE--WYCPSC 360
Cdd:cd15499    2 CSICGGAEARDGNeiLICDKCDKGYHQLCHSPKVRTSPLEGDekWFCSRC 51

PHD finger found in bromodomain adjacent to zinc finger domain protein 2B (BAZ2B); BAZ2B, also termed WALp4, is a bromodomain-containing protein whose biological role is still elusive. It shows high sequence similarly with BAZ2A, which is the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP-and histone H4 tail-dependent fashion. BAZ2B contains a TAM (TIP5/ARBP/MBD) domain, an Apolipophorin-III like domain, a DDT domain, four AT-hooks, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

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gi 162287241 315 CHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVpPEPEWYCPSC 360
Cdd:cd15630    3 CQICRKGDNEELLLLCDGCDKGCHTYCHRPKITTI-PEGDWFCPAC 47

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

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gi 162287241   8 MDGKETHTVnSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGH-TLFDYDVRLNDTIQLL 72
Cdd:cd17053    7 LLTGTVHTL-QVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGDkTLGEYGIKTGDTLYLL 71